OBJECTIVE To investigate the molecular mechanism of Tiaozhong huashi decoction in improving gastroesophageal reflux disease （GERD） by regulating endoplasmic reticulum autophagy in rat esophageal interstitial cells of Cajal （ICC） through p62 signaling pathway.METHODS After establishing a rat GERD model via the weak acid intragastric administration and irregular diet， the rats were randomly divided into model group， western medicine group [1.56 mg/（kg·d） of mosapride， 3.125 mg/（kg·d） of lansoprazole] and low-， medium- and high-dose Tiaozhong huashi decoction [4.713， 9.425， 18.85 g/（kg·d）] groups. A blank group was also set up， with 8 rats in each group. The rats in each group were intragastrically administered with corresponding liquid or normal saline twice a day for 14 days. During the intervention period， the general conditions of rats’ hair， spirit， diet and defecation were observed. After the last gavage， the pathological changes of esophageal tissue and the ultrastructure of ICC were observed. The relative expression and positive expression levels of p62， autophagy-related protein 8 （ATG8）， 200 kDa FAK family kinase-interacting protein （FIP200） and Unc-51 like autophagy activating kinase 1 （ULK1） in esophageal tissue were detected.RESULTS Compared with the blank group， rats in the model group exhibited listlessness； thickening of the esophageal basal layer， elongation of lamina propria papillae with inflammatory cell infiltration； markedly dilated endoplasmic reticulum appearing as round vacuolar cisternae with ribosome detachment； and a small number of accumulated autophagosomes. The relative expression and positive expression levels of p62， ATG8， FIP200， and ULK1 were significantly decreased （ P ＜0.05）. Compared with the model group， the above pathological injuries in the medium- and high-dose Tiaozhong huashi decoction groups had all improved to varying degrees； the damaged endoplasmic reticulum structure was repaired， and no autophagosome accumulation was observed. In particular， the relative expression levels and positive expression levels of p62， ATG8， FIP200， and ULK1 in esophageal tissue of rats in the medium-dose Tiaozhong huashi decoction group were significantly increased （ P ＜0.05）.CONCLUSIONS Tiaozhong huashi decoction ameliorated esophageal mucosal injury in GERD rats， and its mechanism was possibly associated with activation of the p62 signaling pathway and restoration of the endoplasmic reticulum structure， morphology， and autophagic capacity of ICC.

This article reported the process of individualized medication management by a clinical pharmacist in the treatment of a patient with autoimmune pancreatitis(AIP)complicated by a relapse of ulcerative colitis(UC).Upon admission,in collaboration with the clinical pharmacist,the physician formulated a combined treatment plan of oral prednisone and mesalazine based on the patient's condition and the latest research literature.After 3 days of medication,the patient's diarrhea symptoms worsened,and colonoscopy revealed a severe,extensive flare of UC.After discussing,the physician and clinical pharmacist decided to switch the oral prednisone to intravenous methylprednisolone sodium succinate and replace mesalazine suppositories with mesalazine enema.Subsequently,the patient developed a fever and was diagnosed with Clostridiodes difficile infection.After a comprehensive evaluation,the clinical pharmacist recommended the use of metronidazole and implemented careful pharmaceutical monitoring.After 5 days of treatment,the patient's symptoms significantly improved without any adverse reactions.This case highlights the critical role of clinical pharmacists in managing complex clinical situations,particularly in optimizing treatment regimens and ensuring medication safety.It also provides practical experience and guidance for physicians and clinical pharmacists in handling similar cases.

BACKGROUND:Titanium surface micro-nano structure modification is a hot research field in titanium implant surface treatment.The diabetic hyperglycemia environment will affect the stable bonding between titanium implant and bone tissue,so it is necessary to explore the surface micro-nano structure modification to improve the osteogenic activity of titanium implant in high glucose environment.OBJECTIVE:To investigate the effect of gold nanoparticle@mesoporous silica nanoparticles(AuNPs@MSNs)coating on osteogenic activity of osteoblasts under high glucose in vitro.METHODS:Gold nanoparticle suspension and mesoporous silica were prepared respectively,and the two were mixed in deionized water in a certain proportion to prepare gold nanoparticle@mesoporous silica suspension.Titanium sheets were taken and divided into three groups for treatment:the smooth group was treated with water sandpaper;the nanotube group was treated with water sandpaper and then anodized to prepare titanium dioxide nanotube coating,and the experimental group prepared titanium dioxide nanotube coating and then immersed in gold nanoparticle@mesoporous silica suspension to prepare gold nanoparticle@mesoporous silica nanoparticles coating.The microscopic morphology and hydrophilicity of the surface of the three groups of titanium sheets were characterized.Rat bone marrow mesenchymal stem cells were inoculated on the surface of the three groups of titanium sheets.Cell proliferation was detected by cell live/dead fluorescence staining and CCK-8 assay.Cell adhesion was detected by DAPI/phalloidin staining.Rat bone marrow mesenchymal stem cells were inoculated on the surface of the three groups of titanium sheets,and high-glucose osteogenic induction medium was added for culture.Osteogenic differentiation was detected by alkaline phosphatase and Alizarin Red S staining.RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the surface of the titanium sheet in the smooth group was uniform and flat.The titanium dioxide nanotube arrays in the nanotube group were closely arranged on the surface,and the titanium sheet in the experimental group was loaded with gold nanoparticle@mesoporous silica on the surface and inside of the titanium dioxide nanotubes.The hydrophilicity of the titanium sheets in the nanotube group and the experimental group was better than that in the smooth group.(2)The results of cell live/dead fluorescence staining exhibited that the cell viability on the surface of the three groups of titanium sheets was higher than 90%.The results of CCK-8 assay show that the cell proliferation rate in the experimental group was higher than that in the smooth group and the nanotube group.The results of DAPI/phalloidin staining showed that the titanium dioxide nanotube coating and the gold nanoparticle@mesoporous silica nanoparticles coating were more conducive to cell adhesion.(3)The results of alkaline phosphatase and Alizarin Red S staining showed that the alkaline phosphatase activity and extracellular matrix mineralization of the cells on the titanium sheet surface in the experimental group were higher than those in the smooth group and the nanotube group.(4)The results show that the gold nanoparticle@mesoporous silica nanoparticles coating can enhance the biological activity of the titanium surface and promote osteogenic differentiation in a high glucose environment.

This article reported the process of individualized medication management by a clinical pharmacist in the treatment of a patient with autoimmune pancreatitis(AIP)complicated by a relapse of ulcerative colitis(UC).Upon admission,in collaboration with the clinical pharmacist,the physician formulated a combined treatment plan of oral prednisone and mesalazine based on the patient's condition and the latest research literature.After 3 days of medication,the patient's diarrhea symptoms worsened,and colonoscopy revealed a severe,extensive flare of UC.After discussing,the physician and clinical pharmacist decided to switch the oral prednisone to intravenous methylprednisolone sodium succinate and replace mesalazine suppositories with mesalazine enema.Subsequently,the patient developed a fever and was diagnosed with Clostridiodes difficile infection.After a comprehensive evaluation,the clinical pharmacist recommended the use of metronidazole and implemented careful pharmaceutical monitoring.After 5 days of treatment,the patient's symptoms significantly improved without any adverse reactions.This case highlights the critical role of clinical pharmacists in managing complex clinical situations,particularly in optimizing treatment regimens and ensuring medication safety.It also provides practical experience and guidance for physicians and clinical pharmacists in handling similar cases.

BACKGROUND:Titanium surface micro-nano structure modification is a hot research field in titanium implant surface treatment.The diabetic hyperglycemia environment will affect the stable bonding between titanium implant and bone tissue,so it is necessary to explore the surface micro-nano structure modification to improve the osteogenic activity of titanium implant in high glucose environment.OBJECTIVE:To investigate the effect of gold nanoparticle@mesoporous silica nanoparticles(AuNPs@MSNs)coating on osteogenic activity of osteoblasts under high glucose in vitro.METHODS:Gold nanoparticle suspension and mesoporous silica were prepared respectively,and the two were mixed in deionized water in a certain proportion to prepare gold nanoparticle@mesoporous silica suspension.Titanium sheets were taken and divided into three groups for treatment:the smooth group was treated with water sandpaper;the nanotube group was treated with water sandpaper and then anodized to prepare titanium dioxide nanotube coating,and the experimental group prepared titanium dioxide nanotube coating and then immersed in gold nanoparticle@mesoporous silica suspension to prepare gold nanoparticle@mesoporous silica nanoparticles coating.The microscopic morphology and hydrophilicity of the surface of the three groups of titanium sheets were characterized.Rat bone marrow mesenchymal stem cells were inoculated on the surface of the three groups of titanium sheets.Cell proliferation was detected by cell live/dead fluorescence staining and CCK-8 assay.Cell adhesion was detected by DAPI/phalloidin staining.Rat bone marrow mesenchymal stem cells were inoculated on the surface of the three groups of titanium sheets,and high-glucose osteogenic induction medium was added for culture.Osteogenic differentiation was detected by alkaline phosphatase and Alizarin Red S staining.RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the surface of the titanium sheet in the smooth group was uniform and flat.The titanium dioxide nanotube arrays in the nanotube group were closely arranged on the surface,and the titanium sheet in the experimental group was loaded with gold nanoparticle@mesoporous silica on the surface and inside of the titanium dioxide nanotubes.The hydrophilicity of the titanium sheets in the nanotube group and the experimental group was better than that in the smooth group.(2)The results of cell live/dead fluorescence staining exhibited that the cell viability on the surface of the three groups of titanium sheets was higher than 90%.The results of CCK-8 assay show that the cell proliferation rate in the experimental group was higher than that in the smooth group and the nanotube group.The results of DAPI/phalloidin staining showed that the titanium dioxide nanotube coating and the gold nanoparticle@mesoporous silica nanoparticles coating were more conducive to cell adhesion.(3)The results of alkaline phosphatase and Alizarin Red S staining showed that the alkaline phosphatase activity and extracellular matrix mineralization of the cells on the titanium sheet surface in the experimental group were higher than those in the smooth group and the nanotube group.(4)The results show that the gold nanoparticle@mesoporous silica nanoparticles coating can enhance the biological activity of the titanium surface and promote osteogenic differentiation in a high glucose environment.

Acute pancreatitis （AP） is one of the most clinically common acute digestive disorders characterized by quick onset，rapid progression，severe condition，and high mortality. If the disease is not timely intervened in the early stage，it can develop into severe AP in the later stage，which damages the long-term quality of life and brings serious economic burden to patients and their families. However， the pathogenesis of this disease is complex and has not been fully explained. The generation and development of AP is closely related to many signaling pathways. Among them，Toll-like receptor 4（TLR4），as a transmembrane signal transduction receptor，can mediate immune response and inflammatory response，and play a key role in the occurrence and development of AP. Traditional Chinese medicine（TCM）can regulate the TLR4 signaling pathway with multiple targets，multiple effects，and multiple administration methods to inhibit inflammatory response，and effectively intervene in the progression of AP， which has gradually become a new craze for preventing and treating AP. Many studies have shown that TCM has obvious advantages in the prevention and treatment of AP. It can effectively treat AP by regulating TLR4 signaling pathway，strengthening immune resistance and defense，and inhibiting inflammatory response. Despite of the research progress，there is still a lack of comprehensive review on TCM regulation of TLR4 signaling pathway in the treatment of AP. Therefore，the literature on TCM regulation of TLR4 signaling pathway published in recent years was systematically reviewed and elaborated，aiming to provide new ideas for the treatment of AP and further drug development.

Gastroesophageal reflux disease （GERD） is a gastrointestinal motility disorder characterized by the reflux of gastric contents into the esophagus， leading to symptoms such as acid reflux and heartburn. The incidence of GERD is closely associated with psychological disorders， including anxiety and depression. The brain-gut axis， serving as a mediator of the bidirectional connection between the brain and the gastrointestinal tract， plays a crucial role in the occurrence and development of GERD with anxiety and depression. Various therapeutic approaches， including compound Chinese medicine internal therapy （such as Pingchong jiangni decoction， Tiaozhong huashi decoction， etc.）， combination therapy of internal and external Chinese medicine （such as Lianzhi xiere decoction combined with acupoint application， acupuncture at the back segment of governor vessel plus Chinese medication of soothing the liver and gallbladder， etc.）， and combination therapy of internal Chinese and western medicine （including Jianpi shugan decoction combined with rabeprazole， rabeprazole combined with Jianzhong jiangni decoction， etc.）， have been shown to regulate brain-gut peptides， intestinal flora， inflammatory factors and gastrointestinal hormones， thereby effectively alleviating GERD symptoms， anxiety and depression， and enhancing patients’ quality of life.

Objective:To evaluate the effect of combined cognitive and physical intervention on mild cogni-tive impairment(MCI)using meta-analysis.Methods:Five databases including CNKI,PubMed,Web of Science,Cochrane and Embase were retrieved.Randomized Control Trials containing the combined cognitive and physical therapies on MCI were included.Statistical analysis,including the evaluation of the effects on global cognition,memory and executive function or attention,as well as the subgroup analysis were conducted using Stata 15.0.Results:A total of 28 articles was eventually included,with 2 796 participants.Results showed that the effec-tiveness of combined intervention on global cognitive function(SMD=0.68,95％CI:0.39-0.97),memory(SMD=0.35,95％CI:0.01-0.68)as well as executive function or attention(SMD=-0.28,95％CI:-0.51--0.05)were significantly better than the control group.Subgroup analysis indicated that the effects of combined intervention on the above domains of cognitive function among the participants were affected by the intervention mode,control type,whether there were other interventions and intervention frequency.Conclusion:Combined cogni-tive and physical intervention could effectively improve mild cognitive impairment.

Objective:To establish the norm of the Chinese version of Karitane Parenting Confidence Scale (KPCS) in urban areas of China.Methods:From August to December 2017, the parents of 2 216 children (<36 months old) were selected from 15 cities (Beijing, Lianyungang, Hangzhou, Chengdu, Xi′an, Guangzhou, Changsha, Jinan, Guiyang, Ningbo, Dalian, Qinhuangdao, Maanshan, Chongqing and Wuhan) in 14 provinces by stratified random sampling. The general demographic characteristics and parents′ parenting confidence were collected by a self-made questionnaire and KPCS Chinese version. The percentile norm was established. P 3, P10 and P 25 were used as the criteria to define the degree of lack of parenting confidence. Results:The age of mothers was (30.67±4.29). The age of the father was (32.50±4.99) years old. There were 726 (32.76%), 759 (34.25%) and 731 (32.99%) infants in 6-12, 12-23 and 24-35 months old groups. The total scores of P 50, P 25, P 10 and P 3 of KPCS (Chinese version) of infant parents in urban areas in China were 41, 38, 33, and 29 respectively. When the scores of parents were 34-37, 30-33, and ≤ 29, they were judged as mild, moderate, and severe lack of parenting confidence. There was no significant difference in the Chinese version of KPCS between parents of different age groups and parents of different gender (χ2=3.53, P=0.171; χ2=1.41, P=0.236). Each factor score≤ P 3 is defined as the boundary score, and the corresponding boundary scores of "parenting" "support" and "competence" were 13, 9, and 5 respectively. Conclusion:The Chinese version of KPCS can be used to assess the parenting confidence of infants in urban areas of China. It can used as one of the bases for scientific and objective evaluation of the parenting status of families.

Objective:To establish the norm of the Chinese version of Karitane Parenting Confidence Scale (KPCS) in urban areas of China.Methods:From August to December 2017, the parents of 2 216 children (<36 months old) were selected from 15 cities (Beijing, Lianyungang, Hangzhou, Chengdu, Xi′an, Guangzhou, Changsha, Jinan, Guiyang, Ningbo, Dalian, Qinhuangdao, Maanshan, Chongqing and Wuhan) in 14 provinces by stratified random sampling. The general demographic characteristics and parents′ parenting confidence were collected by a self-made questionnaire and KPCS Chinese version. The percentile norm was established. P 3, P10 and P 25 were used as the criteria to define the degree of lack of parenting confidence. Results:The age of mothers was (30.67±4.29). The age of the father was (32.50±4.99) years old. There were 726 (32.76%), 759 (34.25%) and 731 (32.99%) infants in 6-12, 12-23 and 24-35 months old groups. The total scores of P 50, P 25, P 10 and P 3 of KPCS (Chinese version) of infant parents in urban areas in China were 41, 38, 33, and 29 respectively. When the scores of parents were 34-37, 30-33, and ≤ 29, they were judged as mild, moderate, and severe lack of parenting confidence. There was no significant difference in the Chinese version of KPCS between parents of different age groups and parents of different gender (χ2=3.53, P=0.171; χ2=1.41, P=0.236). Each factor score≤ P 3 is defined as the boundary score, and the corresponding boundary scores of "parenting" "support" and "competence" were 13, 9, and 5 respectively. Conclusion:The Chinese version of KPCS can be used to assess the parenting confidence of infants in urban areas of China. It can used as one of the bases for scientific and objective evaluation of the parenting status of families.